The goal of this project is to define the genetic control mechanisms that regulate the activity of renin in the submaxillary gland of the mouse and to characterize the mechanisms by which steroid hormones interdigitate with regulatory genes to influence renin activity. Information gained in this study will provide the foundation for subsequent investigation of the regulation of renin in the kidney. Inbred and recombinant inbred strains of mice will be used to identify a structural mutant of renin, locate the structural gene on the mouse chromosome, determine the biochemical nature of the mutation and investigate the structural relationship between kidney and submaxillary gland renin. Additional biochemical and genetic experiments are designed to determine the relationship between the renin structural gene and Rnr, a regulatory gene that mediates the susceptibility of submaxillary gland renin to induction by androgens and to establish the mechanism by which RNr controls renin activity. The genetic control of strain specific differences in posttranslational processing, storage, and release of this biologically and clinically important secretory protein will also be investigated.